AB0468 DRUG RETENTION AND SAFETY OF JANUS KINASE INHIBITORS IN RHEUMATOID ARTHRITIS PATIENTS - REAL WORLD EXPERIENCE FROM A SINGLE CENTRE IN UK
Authors: H. Muhammed, F. Waliul, A. Ajibade, S. Pelia, G. Hirsch, T. Adizie, T. Sheeran, S. Venkatachalam
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Tofacitinib, baricitinib, upadacitinib and filgotinib are the Janus kinase inhibitors (JAKi) approved for the treatment of rheumatoid arthritis (RA) in the UK. We report our real-world experience in a cohort of RA patients commenced on JAKi in a regional centre in the UK. <h3>Objectives</h3> To study drug retention rates and adverse events of JAKi in RA patients in the real- world scenario. <h3>Methods</h3> Data of patients with RA initiated on JAKi from February 2018 to August 2022 were retrospectively collected from hospital and primary care records. Kaplan-Meier curve was plotted for the cumulative drug retention rate. Crude event rates for various adverse events were calculated per 100 patient-years. Hazard ratios were calculated for adverse events for tofacitinib vs baricitinib after adjusting for baseline variability using inverse probability of treatment weighting (IPTW). Statistical analysis was done using R studio. <h3>Results</h3> During the study period 356 patients were initiated on JAKi (Baricitinib: 266, Tofacitinib: 48, Upadacitinib: 33 and Filgotinib: 9). Baseline characteristics of patients are given in Table 1. Over 734.6 patient-years follow up 92 (25.6%) discontinued JAKi. Drug retention rate at 2 years, 3 years and 4 years was 74.2%, 67.5% and 61.5% respectively (Figure 1). Most common reason for discontinuation was lack/loss of response (42.3%). Infections led to discontinuation in 13 patients and cardiovascular events in 5 patients. Lymphopenia, rash, oral ulcer, anemia, weight gain, high cholesterol, diverticulitis, and lymphedema were the other adverse events which resulted in discontinuation. Ten patients died while on treatment with JAKi. Six patients had a major adverse cardiovascular event (MACE) - 4 acute coronary events and 2 strokes. Nine patients had a venous thromboembolic event (VTE) while one patient had central retinal artery occlusion. Event rates for MACE and VTE were 0.8(0.3-1.7) and 1.2(0.5-2.3) respectively. Herpes zoster (HZ) occurred in 13 patients with an event rate of 1.8(1.0-3.1). Incident malignancies were noted in 14 patients on JAKi. Event rate was 1.1(0.5-2.2) for malignancies excluding 6 non-melanoma skin cancers. There were no statistically significant differences in the incidence of adverse events between tofacitinib and baricitinib. Hazard ratios for discontinuation, MACE, Pulmonary embolism, HZ, and malignancy were 0.7 (0.4-1.4), 2.0 (0.3-10.8), 0.2(0.02-1.4), 0.8(0.2-3.3) and 1.2(0.3-5.0) respectively for tofacitinib compared to baricitinib. Upadacitinib and filgotinib had shorter follow up duration to draw any meaningful conclusion. <h3>Conclusion</h3> JAKi in this real-world population of RA patients had high persistence rates. MACE, VTE, HZ and infections remain adverse events of concern. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.